title: Involvement of ER stress in apoptosis induced by sialic acid-binding lectin (leczyme) from bullfrog eggs.
abstract: Sialic-acid binding lectin (SBL) isolated from bullfrog (Rana catesbeiana) oocytes is a multifunctional protein which has lectin activity, ribonuclease activity and cancer-selective antitumor activity. It has been reported that SBL induces apoptosis accompanied by rigid mitochondrial perturbation, which indicates mediation of the intrinsic pathway. However, the mechanism of the antitumor effect of SBL has not been fully elucidated. We report, here, that ER stress is evoked in SBL-treated cells. We show that caspase-4, an initiator caspase of ER stress-mediated apoptosis was activated, and inhibition of caspase-4 resulted in significant attenuation of apoptosis induced by SBL. We analyzed the precise mechanism of activation of the caspase cascade induced by SBL, and found that caspase-9 and -4 are activated upstream of activation of caspase-8. Further study revealed that SBL induces the mitochondrial and ER stress-mediated pathways independently. It is noteworthy that SBL can induce cancer-selective apoptosis by multiple apoptotic signaling pathways, and it can serve as a candidate molecule for anticancer drugs in a novel field.
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Tatsuta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hosono
authors.forename: Yuki
authors.initials: Y
authors.lastname: Miura
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugawara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kariya
authors.forename: Senitiroh
authors.initials: S
authors.lastname: Hakomori
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nitta
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D053471:Caspases, Initiator / Q000378:metabolism; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010619:Phenazines / Q000494:pharmacology; D011892:Rana catesbeiana; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism*; D015398:Signal Transduction; D013141:Spiro Compounds / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology
chemical_list: D061945:Caspase Inhibitors; D009842:Oligopeptides; D010619:Phenazines; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013141:Spiro Compounds; D013256:Steroids; C403754:benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone; C454806:cephalostatin I; C093516:CASP4 protein, human; D053181:Caspase 8; D053453:Caspase 9; D053471:Caspases, Initiator